TY - THES A1 - Offenberger, Wolfgang T1 - Hochaufgelöste Magnetresonanz-Bildgebung der Mäuseaorta zur Bestimmung der Dynamik funktioneller Parameter durch Laufrad-Training bei ApoE-Knock-Out-Mäusen T1 - High-Resolution Magnetic Resonance Imaging of the Murine Aorta in the evaluation of dynamic functional vessel changes through running wheel exercise in ApoE-knock-out mice. N2 - Einführung: Atherosklerose ist eine führende Ursache von Morbidität und Mortalität weltweit. Die ApoE-Knock-Out-Maus (ApoE-/-) ist das wichtigste Tiermodell für das Studium der Atherosklerose und von Interventionen auf diese Erkrankung. Mittels hochaufgelöster Magnet-Resonanz-Bildgebung ist es möglich, eine nicht-invasive in-vivo Gefäß-Charakterisierung bei Mäusen durchzuführen. In dieser Arbeit wurden die Auswirkungen von Sport auf die Gefäßfunktion der Aorta ascendens und abdominalis bei ApoE-/--Mäusen mittels hochaufgelöster MR-Cine-FLASH-Bildgebung untersucht. Methodik und Ergebnisse: 18 ApoE-/--Mäuse mit oder ohne Lipid-reicher „Western Type Diet“ (WTD) führten 4-6 Wochen lang Laufrad-Training durch. Vor Laufrad-Training wurde zweimal (Validität) und nach Laufrad-Training einmal mittels EKG- und Atmungs-getriggerter Magnet-Resonanz-Cine-FLASH-Bildgebung an einem 7-Tesla-Scanner unter Isofluran-Inhalationsnarkose die Compliance von Aorta ascendens und abdominalis gemessen. Aufnahme-Parameter: TR/TE = 4,3/1,4 ms; Field of View (FOV) = 3,0 x 3,0 cm2; Matrixgröße = 256 x 256; Pixel-Größe = (FOV / Matrix) = (30 mm / 256) = 0,0117 mm2; Schichtdicke = 1,0 mm, Auflösung von 0,0137 mm3. Die Resultate wurden verglichen mit 9 Wildtyp-Mäusen vom Stamm C57BL/6J, und mittels der Auswerte-Software Interactive Data Language (IDL) prozessiert. Es zeigten sich gewisse positive Effekte hinsichtlich Compliance der Aorta ascendens durch Sport, die Ergebnisse waren für ApoE-/--Mäuse ohne WTD jedoch wesentlich konsistenter als für ApoE-/--Mäuse mit WTD, wo die Ergebnisse teilweise widersprüchlich erscheinen. Dasselbe gilt für die Aorta abdominalis, die sich zudem in vielen MR-Untersuchungen nicht auswerten ließ, was zu nicht interpretierbaren Ergebnissen führte. Bezüglich der Validität zeigte sich eine sehr hohe Intra-Observer- und Inter-Observer-Übereinstimmung der Ergebnisse, dies zeigte sich auch für Messungen zu zwei Zeitpunkten. Schlussfolgerung: Die Ergebnisse erscheinen insgesamt kritisch beleuchtet nicht signifikant und zeigen allenfalls Besserungs-Tendenzen für die Compliance der Aorta ascendens und abdominalis bei ApoE-/--Mäusen durch Sport. Weitere MRT-Studien mit höheren Feldstärken und weiterentwickelten MR-Protokollen sind notwendig, um die Aussage dieser Doktorarbeit, dass Atherosklerose bei ApoE-/--Mäusen durch Sport teilweise reversibel ist, zu bestätigen. N2 - Introduction: Atherosclerosis is a leading cause of morbidity and mortality throughout the world. The apoE-knock-out mice is the most important animal model of studies on atherosclerosis and of interventions on atherosclerotic diseases. High-resolution magnetic resonance imaging (MRI) allows to non-invasively provide in-vivo murine vessel characterization. This work aims to determine the impact of sports training on vessel function of the ascending and abdominal aorta in hypercholesterinemic apoE-knock-out mice by high-resolution CINE MR-Flash-imaging. Methods and Results: 18 ApoE-knock-out mice with or without lipid-rich "Western Type Diet" (WTD) performed 4-6 weeks of running wheel training. Using ECG- and breathing-triggered CINE MR-Flash-imaging on a 7-Tesla-MR-Scanner under isofluran anesthesia the compliance of the ascending and abdominal aorta was examined twice (validity) before and once after running wheel training. MR-paramter: TR/TE = 4,3/1,4 ms; field of view 3,0 x 3,0 cm2; matric size 256-256; Pixel size = 0,0117 mm2; slice thickness 1,0 mm, resulting resolution 0,0137 mm3. The results were compared with 9 wild type mice (C57Bl/6J), and analyzed by means of software (Interactive Data Language, IDL). The results showed positive effects in respect to the compliance of the ascending aorta after training, being much more consistent for apoE-knock out mice without WTD than in mice with WTD, where the results seem contradictory. The same goes for the abdominal aorta, where many MRI-examinations were not evaluable. A high inter- and intra-observer-validity could be shown for analyzation of the results. Conclusion: The results do not seem to be significant and at most show a tendency of improvement in respect to the complicance of the ascending and abdominal aorta in apoE-knock-out mice after training. Further MRI studies with higher strengths of field and advanced MR-protocolls will be necessary to confirm the results of this work, that atherosclerosis can be partially reversible through exercise training. KW - Magnetresonanztomographie KW - NMR-Tomographie KW - Brustaorta KW - Arteriosklerose KW - Elastizität KW - Draisine KW - Sport KW - Training KW - ApoE-Knock-Out-Maus KW - hypercholesterinämie KW - compliance KW - MRI KW - magnetic resonance imaging KW - atherosclerosis KW - ApoE-knock-out mice KW - hypercholesterolemia KW - exercise KW - training KW - running wheel KW - thoracic aorta Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-35146 ER - TY - JOUR A1 - Kraft, Peter A1 - Schuhmann, Michael K. A1 - Garz, Cornelia A1 - Jandke, Solveig A1 - Urlaub, Daniela A1 - Mencl, Stine A1 - Zernecke, Alma A1 - Heinze, Hans-Jochen A1 - Carare, Roxana O. A1 - Kleinschnitz, Christoph A1 - Schreiber, Stefanie T1 - Hypercholesterolemia induced cerebral small vessel disease JF - PLoS ONE N2 - Background While hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr\(^{−/-}\) mouse model. Methods We used Ldlr\(^{−/-}\) mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr\(^{−/-}\) mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds. Results We found a significant increase in the number of erythrocyte stases in 6 months old Ldlr\(^{−/-}\) mice compared to all other groups (P < 0.05). Ldlr\(^{−/-}\) animals aged 12 months showed the highest number of thrombotic occlusions while in WT animals hardly any occlusions could be observed (P < 0.001). Compared to WT mice, Ldlr\(^{−/-}\) mice did not display significant gray matter BBB breakdown. Microhemorrhages were observed in one Ldlr\(^{−/-}\) mouse that was 6 months old. Results did not differ when considering subcortical and cortical regions. Conclusions In Ldlr\(^{−/-}\) mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr\(^{−/-}\) mice appear to be an adequate animal model for research into CSVD. KW - hypercholesterolemia KW - cerebral small vessel disease KW - mouse model KW - histology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170493 VL - 12 IS - 8 ER - TY - JOUR A1 - Krieter, Detlef H. A1 - Jeyaseelan, Jarline A1 - Rüth, Marieke A1 - Lemke, Horst-Dieter A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Clinical hemocompatibility of double-filtration lipoprotein apheresis comparing polyethersulfone and ethylene-vinyl alcohol copolymer membranes JF - Artificial Organs N2 - Activation of the complement system and leukocytes by blood–membrane interactions may further promote arteriosclerosis typically present in patients on lipoprotein apheresis. As clinical data on the hemocompatibility of lipoprotein apheresis are scarce, a controlled clinical study comparing two different types of plasma separation and fractionation membranes used in double-filtration lipoprotein apheresis was urgently needed, as its outcome may influence clinical decision-making. In a prospective, randomized, crossover controlled trial, eight patients on double-filtration lipoprotein apheresis were subjected to one treatment with recent polyethersulfone (PES) plasma separation and fractionation membranes and one control treatment using a set of ethylene-vinyl alcohol copolymer (EVAL) membranes. White blood cell (WBC) and platelet (PC) counts, complement factor C5a and thrombin–antithrombin III (TAT) concentrations were determined in samples drawn at defined times from different sites of the extracorporeal blood and plasma circuit. With a nadir at 25 minutes, WBCs in EVAL decreased to 33.5 ± 10.7% of baseline compared with 63.8 ± 22.0% at 20 minutes in PES (P < .001). The maximum C5a levels in venous blood reentering the patients were measured at 30 minutes, being 30.0 ± 11.2 µg/L with EVAL and 12.3 ± 9.0 µg/L with PES (P < .05). The highest C5a concentrations were found in plasma after the plasma filters (EVAL 56.1 ± 22.0 µg/L at 15 minutes vs PES 23.3 ± 15.2 µg/L at 10 minutes; P < .001). PC did not significantly decrease over time with both membrane types, whereas TAT levels did not rise until the end of the treatment without differences between membranes. Regarding lipoprotein(a) and low-density lipoprotein (LDL) cholesterol removal, both membrane sets performed equally. Compared with EVAL, PES membranes cause less leukocyte and complement system activation, the classical parameters of hemocompatibility of extracorporeal treatment procedures, at identical treatment efficacy. Better hemocompatibility may avoid inflammation-promoting effects through blood–material interactions in patients requiring double-filtration lipoprotein apheresis. KW - lipoprotein(a) KW - biocompatibility KW - fractionation membranev KW - hypercholesterolemia KW - LDL cholesterol KW - lipoprotein apheresis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258307 VL - 45 IS - 9 ER -